ROLE OF ANTI-INFLAMMATORY DRUGS IN SURGERY

3. Introduction
Inflammation is a protective immunovascular
response that involves immune cells, blood vessels, and
molecular mediators.
Can be CAUSED by numerous stimuliincluding:
•Antigen-antibody interaction
•Thermal and physical injury
•Microbial invasion
•Physical damage
•Immune reactions

4. Signsofinflammation
Redness–due to vasodilation of capillariesto
increase blood flow.
Heat - due to effect on thermoregulatory site of
the brain.
Swelling– due to Increased vascularpermeability
and influx of plasma proteins and phagocytic
cells into the tissuespaces
Pain– due to
-Hyperalgesia, sensitization of nociceptors
-local release of pain inducersand
-increased tissue pressure

5. Inflammatory responses occur in
three distinct phases:
1. An acute transient phase, characterized by:
– local vasodilation and its resulting increased bloodflow
causesthe redness (rubor) and increased heat (calor)
– Increased permeability of the blood vessels results in the
leakage of plasma proteins and fluid into the tissue (edema),
which manifests itself asswelling.
1. A delayed phase, most prominently characterized by:
– infiltration of leukocytes and phagocytic cells to the
injured /inflammed tissue
2. A chronic proliferative phase, in which:
– tissue degeneration and fibrosis occur

6. Mediators of the inflammatory response
 Prostaglandins
PGE2 - promote Vasodilation,Directly Cause Pain and
Induces Fever
PGI2 - increase vascular permeability, enhance pain
producing properties of bradykinin.
Histamine – Secreted from mast cell .Histamine
causesdilation and increased permeability of
capillaries.
Plasma proteases(Bradykinin)- Avasoactive protein
which is able to induce vasodilation, increasevascular
permeability, causesmooth muscle contraction,and
induce pain.
(C5H9N3)
Bradykinin
C50H73N15O11

7. Leukotrienes
- increase vascular permeability andleakiness.
- increase mobilization of endogenous mediators ofinflammation
Thromboxane A2 (TXA2)- Thromboxane is a member of the family
of lipids known as eicosanoids. The two major thromboxanes are
thromboxane A2and thromboxane B2.
causeplatelets to aggregate
causes vasoconstriction
causessmooth muscle contraction
enhances function of inflammatorycells.
C20H32O5

8. Typesof anti-inflammatory drugs
Steroidalanti-
inflammatorydrugs
Non-steroidalanti-
inflammatory drug
- Cortisone
- Hydrocortisone
- Acetaminophen
- Aspirin

10. Steroidalanti-inflammatory drugs
(SAIDs)
 Thesteroids are compounds with glucocorticoid activity,and
are more powerful drugs thanNSAIDs.
 - Containing steroid moiety in their structure.
 Derived from cholesterol.
Glucocorticoids (GC)
CortisoneHydrocortisone C21H28O5C21H30O5

11. Glucocorticoids (GC)
Mechanism of Action :
They act by indirect inhibition of the enzyme phospholipaseA2
which activate synthesis of arachidonic acid with subsequent
formation of prostaglandins.
They induce synthesis of a protein “lipocortin-1” which has
the inhibitory effect on phospholipaseA2.
They enter in to the cell and reach nucleus.

12. phospholipaseA2
GC inhibition

13. Hyperglycemia due to increased gluconeogensis, insulin resistance,
and impaired glucose tolerance ("steroid diabetes");
Redistribution of body fat: moon face, buffalo hump and truncal
obesity.
 Muscle breakdown (proteolysis),weakness; reduced muscle mass.
 Increased plasma amino acids, increased urea formation;
Growth failure,
Adrenal insufficiency.
 Glaucoma due to increased cranial pressure.
SideEffects :

14. Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs)are achemically
heterogeneous group of compounds that provide unmistakable and
significant health benefits in the treatment of pain and inflammation.
TheNSAIDscan be sub-classified on the basisof chemical structure
asfollows:
 Salicylates
 Propionic Acids(Profens)
 Aryl and HeteroarylaceticAcids
Oxicams(“EnolAcids”)
Anilides
In general, NSAIDsstructurally consist of an
carboxylic acid, enols attached to aplanar,
aromatic functionality.

15. GeneralMechanismof NSAID Action
The primary action of NSAIDsis the inhibition of the COXenzyme,
by inhibiting this enzyme the production of prostaglandins are also
inhibited. TheCOXenzyme synthesised prostaglandins from fatty
acids suchasarachidonic acid.
Most NSAIDsinhibit both major forms of the COXenzyme, however
all are still considered toxic. Newer drugs which are believed to be
COX-2specific are relatively safer in chronicuse.

17. Besidesfrom the inhibition of the COXenzyme, otheractions
include:
Inhibit superoxides (toxic) and free radicals.
Inhibit Bradykinin production (APeptide which dilates
blood vessels,lowering blood pressure)
Inhibits metalloproteinases (Proteolytic enzymes whose
catalytic mechanism involves ametal)
 Antagonises interleukin-1 and tumour necrosisfactor.
Other Actionsof NSAIDs

19. CommonlyUsedNSAIDsandtheir
properties
Aspirin(Acetylsalicylic acid)
Aspirin is apotent anti-inflammatory drug with
mild central analgesic and antipyretic actions. It is
readily absorbed from the stomach and small
intestine, an acid drug is well absorbed in anacidic
environment. It is metabolised by tissue /plasma
esterases.Aspirin may also be used in low doses,
daily to prevent plateletaggregation.
C9H8O4
Aspirin

20. Action of aspirin
Aspirin and nonselective NSAIDsproduce inhibition of platelet
function via their inhibition of COX1.In the caseof aspirin, the
inhibition is irreversible, sothe effect on platelet function
continues for the life of the affected platelet
Aspirin-like drugs act byinhibiting
the activity of the cyclooxygenase
(COX)enzyme.
COX-1are implicated in the
maintenance of normalphysiological
function and have a'cytoprotective'
action in the stomach. COX-2
expression is normally low butis
induced by inflammatory stimuliand
cytokines.
Mechanism

21. Phenylbutazone is the most widely usedNSAIDin equine
medicine; however it is extremely toxic inhumans. Dueto
the acidity of the drug, it is readily absorbed from the
stomach or duodenum. Phenylbutazone metabolites are
weak acids and therefore preferably excreted in alkaline
urine.
Phenylbutazone
Meloxicam
Meloxicam is asimilar drug, but with ashorter half-life(30-
40 hours). It is thought to havegreater potency for COX-2
than COX-1therefore side-effects may be less.It is also
thought to be chondroprotective (Theslowing of
degradation of articularcartilage)
Meloxicam
C H N OPhenylbutazone
19 20 2 2
C14H13N3O4S2

22. Meclofenamic acid is apotent anti-inflammatory, anti-
pyretic analgesic. It is more potent than aspirin but similar in
effect. Aswell asinhibiting COXenzymesit hasfound to be a
prostaglandin antagonist, interacting with prostaglandin
receptors. It therefore prevents the action of prostaglandin
already present possibly exerting amore rapid reductionof
inflammation.
Meclofenamic Acid
MeclofenamicAcid
Carprofen
C14H11Cl2NO2
Carprofen
Carprofen is apotent anti-inflammatory drug, but is aweak
inhibitor of COX.Its mode of action is not yet known but it
significantly inhibits neutrophil migration. Dueto weak
inhibition of COX,toxicity of Carprofen tends tobe low.
C15H12ClNO2
All thisanti-inflammatory drugshavesimilar mechanismas aspirin.

23. Mild to moderate inflammatorylesions and
associated pain
 Acute inflammation andpain
 Joint inflammation andpain
Suppression of pulmonaryoedema
 Endotoxaemia
 Anti-thrombic
Whento UseNSAIDs

24.  Gastricirritation and ulceration
 Vomitingand diarrhoea
 Hepatotoxicity
 Renalpapillarynecrosis,chronic nephritis
 Bonemarrow disturbance
 Skinrashes
 Respiratorydistress
SideEffectsof NSAIDs

25. Conclusions
 Anti inflammatory drugs plays pivotal role in preventing
inflammation either by affecting inflammatory mediators or
by modifying enzymes required for the synthesis of these
mediators.
 The understanding of the pivotal role of inflammation in
seemingly unrelated diseases has resulted in the use and
development of new anti-inflammatoryagents.